Research Areas

Viral Regulatory Proteins

The genome of the AIDS-virus, the human immunodeficiency virus type 1 (HIV-1), encodes in addition to the viral structural proteins (Gag, Pol, Env) also various regulatory proteins. The essential Rev trans-activator is a nucleocytoplasmic shuttle protein that mediates the nuclear export of unspliced and incompletely-spliced retroviral mRNAs. Rev-dependent nuclear mRNA export is mediated by a series of host cell factors that either directly or indirectly bind to this retroviral regulator. In this project we analyze the mode-of-action of HIV-1 Rev in detail. In particular, the interaction of Rev with its cellular cofactors is investigated.

Gene expression of Herpes Simplex-Viruses is regulated in a distinct, highly coordinated and sequential fashion. The first genes to be expressed are the alpha- or immediate-early (IE) genes, which encode largely regulatory proteins that govern the subsequent expression of the beta- or delayed-early (DE) genes. Both, alpha- and beta-gene products are then required for expression of the gamma- or late (L) genes that mainly encode structural proteins. Particularly the IE gene products, also termed “infected cell proteins” (ICPs), encode frequently multifunctional trans-acting regulators. In this project the mode-of-action of various HSV ICPs, particularly their interaction with factors of the host cell, is investigated.

Antiviral Strategies

The efficient inhibition of the HIV-1 life cycle by highly active antiretroviral therapy (HAART) has been shown to profoundly improve the morbidity and mortality among HIV-1-infected patients. Current routine drug regimens typically consist of various combinations of compounds that target the viral proteins reverse transcriptase (RT), protease (PR) and integrase (IN), or virus entry. Unfortunately, in a growing number of patients long-term HAART is accompanied by significant toxic side effects. In addition, HIV-1 can acquire resistance to all HAART medicines, and occurrence of multidrug (HAART)-resistant HIV-1 strains is becoming a growing problem.

In this project the HIV-1 life-cycle is investigated with respect to the identification of novel cellular drug-targets that allow inhibition of otherwise multidrug-resistant virus strains. Moreover, advanced antiretroviral strategies concentrate on the investigation of HIV-1 sequence-specific recombinases (Tre-recombinases) for excision of integrated proviral DNA, thereby reversing HIV infection. Finally, for inhibition of sexual HIV transmission novel antiviral microbizides are explored.

Intracellular transport of macromolecules / RNA processing

The transport of macromolecules (e.g. RNA, protein) within cells is a highly regulated process. Therefore, the interaction of signal sequences in the respective transport cargo with various adaptors, cofactors and transport-factors is of significant importance. In particular, the regulation of the nuclear export of mRNAs is not fully understood yet.
In this project the nucleocytoplasmic translocation of cellular mRNAs in human immune cells (e.g. dendritic cells; DC) is analyzed and compared to viral mRNA transport (e.g. to the transport of HIV-1 Rev-regulated RNAs).